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Insect defenses point the way to defeating bacterial antibiotic resistance

Insects dominate the animal kingdom, both in terms of numbers and variety. One reason for their success is their remarkably swift and effective system of defense against infections, which differs dramatically from the immune systems of higher-order animals, including humans. Key to the insect immune system is an array of small antimicrobial peptide molecules. Most act, in essence, by latching on to the outer or inner membranes of bacteria and punching holes in the membranes, thereby killing the bacteria.

Now, in a new study, scientists at The Wistar Institute have identified an intracellular target for one of these antimicrobial molecules first isolated from a European sap-sucking insect. The molecule itself is currently being evaluated for its potential as an antibiotic in mammals, including humans. Knowledge of the receptor, however, may make it possible to develop an entirely new class of antibiotics, each rationally designed to fight a specific disease-causing bacterium or fungus. The new findings were published electronically on October 21 in the journal Biochemistry.

"Insects often live in hostile environments, and they are not very long-lived," says Wistar associate professor Laszlo Otvos Jr., Ph.D., lead author on the study. "So they need a rapid way to kill bacteria. In earlier work, we and others discovered several powerful antibiotic molecules used by flies, bees, and other insects to defend themselves against infection. In the current study, we identified the receptor for one of these molecules, which is potentially much more significant. With knowledge of the receptor, the doors are open to developing strain-specific antibiotics."

The new receptor is a heat shock protein referred to as DnaK. Heat shock proteins, in both bacteria and animals, play an all-important role during infections that produce fevers. Fevers cause the proteins that make up all cells to become misshapen, in some cases destroying their ability to do the work fo
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
22-Oct-2000


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